Global burden and trends of lower extremity peripheral arterial disease, 1990–2021: findings from GBD 2021

Background Lower extremity peripheral arterial disease (LEPAD) is a major atherosclerotic condition in ageing populations, contributing to mobility loss, disability, and excess cardiovascular risk. Using modelled estimates from the Global Burden of Disease (GBD) 2021 study, we assessed global, regional, and national LEPAD burden from 1990 to 2021 and projected age-standardised trends to 2040. Methods Modelled estimates of LEPAD prevalence, incidence, deaths, and disability-adjusted life years (DALYs) were extracted from the GBD 2021 study for 204 countries and territories and stratified by age, sex, and socio-demographic index (SDI). Unless otherwise stated, all rates are age-standardised using the GBD world standard population and are reported per 100,000 population with 95% uncertainty intervals (UIs). Temporal trends were summarised using estimated annual percentage change (EAPC), risk-attributable burdens were assessed using GBD comparative risk assessment outputs, and autoregressive integrated moving average (ARIMA) models were used for trend-based projections. Results In 2021, 113.7 million (95% UI 98.5–131.2) people were living with LEPAD worldwide, with 10.0 million (8.7–11.6) incident cases, 67,700 (59,900–74,300) deaths, and 1.56 million (1.27–2.05) DALYs. The ASPR, ASIR, ASDR, and age-standardised DALY rate were 1,326.5 (1,153.8–1,526.5), 115.4 (100.0–132.7), 0.8 (0.7–0.9), and 18.6 (15.2–24.2) per 100,000 population, respectively. From 1990 to 2021, age-standardised death and DALY rates declined overall, whereas absolute case numbers increased. High-SDI regions had the highest age-standardised prevalence and incidence rates, while low- and low-middle-SDI regions showed less favourable temporal trends. High fasting plasma glucose and kidney dysfunction were the largest modelled contributors to LEPAD-related deaths and DALYs. ARIMA projections suggested a possible increase in ASPR through 2040, although these forecasts should be interpreted as descriptive trend extrapolations. Conclusions LEPAD remains a substantial and unevenly distributed global health burden. In the context of population ageing and multimorbidity, prevention strategies should prioritise early detection among older adults and integrated control of cardiometabolic and renal risk factors, particularly in lower-resource settings.